POS0817 THE ROLE OF IGG N-LINKED SIALYLATION AND GALACTOSYLATION IN PRIMARY SJÖGREN’S SYNDROME IN ITS POTENTIAL AS A MARKER OF DISEASE STATE AND DISEASE ACTIVITY
Authors: H. Achten, L. Deroo, K. De Boeck, M. Jarlborg, T. Decruy, J. Deprez, E. Dumas, D. Elewaut, I. Peene
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Primary Sjögren’s Syndrome (pSS) is characterized by the presence of antibodies (Ab). Their effector function mainly depends upon the glycan structures attached to their Fc-fragment. Our study is the first to address the value of IgG glycosylation profiles in relation to disease state, salivary gland ultrasound (SGUS) and auto-Ab in patients with probable (prob pSS) and definite pSS (def pSS). <h3>Objectives</h3> To investigate N-glycosylation of IgG in patients from the Belgian Sjögren’s Syndrome Transitial Trial (BeSSTT) in relation to pSS state, disease activity, SGUS and the presence of Ab to SSA/Ro52, SSA/Ro60 and SSB. <h3>Methods</h3> The relative amount of sialylated (sial) and galactosylated (gal) IgG was determined by capillary electrophoresis after the endo-S glycosidase assay. 314 sera of the BeSSTT, an observational cohort of patients with def pSS, fulfilling the 2016 ACR/EULAR classification criteria, and of patients with suspected pSS due to presence of either objective sicca or one immunological criterion, were used. Groups were made based on the presence or absence of sicca complaints, objective sicca, anti-SSA Ab and histopathology focus score. SGUS by Hocevar was categorized in negative (0-14), low positive (15-26) and high positive (27-48)[1]. Disease activity using the Eular Sjögren’s Syndrome disease activity index (ESSDAI) was categorized in low (0-4), moderate (5-13) and high (14-123). Differences in sial and gal IgG levels were determined using One-way ANOVA and Kruskal-Wallis testing. P-values ≤0.05 were considered statistically significant. Bonferroni correction was applied. <h3>Results</h3> Disease state was addressed in well-defined groups: patients with only sicca complaints, patients with only objective sicca, patients with only anti-SSA/SSB reactivity (prob pSS) and patients with def pSS. Def pSS patients had a significantly lower median percentage of sial and gal IgG compared to patients with only sicca complaints, only objective sicca or only anti-SSA Ab. No significant difference in sial and gal IgG was seen between the latter three groups (Figure 1). Patients with high ESSDAI had a significantly lower percentage of sial and gal IgG versus those with low ESSDAI. In high positive SGUS-score, a significantly lower median percentage of sial IgG and a lower percentage of gal IgG was noted compared to negative or low positive Hocevar score (Figure 1). Mono-anti-Ro52 reactivity, double-anti-Ro52Ro60 reactivity or triple-anti-Ro52Ro60 SSB reactivity had a significantly lower percentage of sial and gal IgG compared to anti-SSA/SSB negative. Strikingly, anti-Ro5260+ and anti-Ro52Ro60 SSB+ had a significantly lower percentage of sial and gal IgG compared to mono anti-Ro60 (Figure 1). <h3>Conclusion</h3> These results indicate that disease state, disease activity, salivary gland involvement and serology profile is strongly associated with different levels of sial and gal IgG in pSS. This highlights the potential role for glycosylation as diagnostic marker and biomarker and its potential role in the pSS pathophysiology. <h3>Reference</h3> [1]Mossel E, et al. J Rheumatol. 2021 May;48(5):717-727 <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.